Theoretical study on the interaction of titanocene dichloride with deoxyguanosine monophosphate

The completely hydrolyzed titanocene dichloride, [Cp2Ti(H2O)2]2+ binding to guanine (G) and phosphate group sites of DNA were investigated by DFT method, with using deoxyguanosine monophosphate (dGMP) as incoming ligand. In the first substitutions, the calculations reveal that the diaquated titanocene binding to O6 shows the lowest activation free energy with 17.9 kcal/mol, closely followed by N7 is 20.5 kcal/mol and the O of phosphate group is 26.3 kcal/mol, respectively. It was also found that all the titanation processes are mildly endothermic. In addition, for the Ti–B(dGMP) in all separated products, the bond dissociation free energies (BDFE) of Ti–O(P, P = phosphate) is higher than those of Ti–N7/O6. In the second substitutions, the reactions leading to the didentate adducts are considered. For bidentate-bridging N7, O6 binding mode, the path of the metal Ti binding to O6 has the lower activation free energy (11.3 kcal/mol) than that of the metal Ti binding to N7 (15.3 kcal/mol). For the bidentate-bridging N7, O(P) binding mode, the path of the metal Ti binding to O(P) has the lower activation free energies (25.3 kcal/mol) than that of the metal Ti binding to N7 (26.2 kcal/mol).